B cell-specific knockout of AID protects against atherosclerosis.
Sci Rep
; 13(1): 8723, 2023 05 30.
Article
in En
| MEDLINE
| ID: mdl-37253865
Antigen-naive IgM-producing B cells are atheroprotective, whereas mature B cells producing class-switched antibodies promote atherosclerosis. Activation-induced cytidine deaminase (AID), which mediates class switch recombination (CSR), would thus be expected to foster atherosclerosis. Yet, AID also plays a major role in the establishment of B cell tolerance. We sought to define whether AID affects atherosclerotic plaque formation. We generated Ldlr-/- chimeras transplanted with bone marrow from Aicda-/- or wild-type (WT) mice, fed a HFD for 14 weeks. Decreased B cell maturation in Ldlr-/-Aicda-/- mice was demonstrated by 50% reduction in splenic and aortic BAFFR expression, a key signaling component of B2 cell maturation. This was associated with increased plasma IgM in Ldlr-/-Aicda-/- compared with Ldlr-/-WT animals. Importantly, Ldlr-/-Aicda-/- mice had reduced atherosclerotic lesion area (0.20 ± 0.03mm2) compared with Ldlr-/-WT (0.30 ± 0.04mm2, P < 0.05), although no differences in plaque composition were noted between groups. In addition, immunofluorescence analysis revealed increased splenic B and T cell areas independent of cell number. AID depletion directly inhibits atherosclerotic plaque formation.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cytidine Deaminase
/
Atherosclerosis
/
Plaque, Atherosclerotic
Limits:
Animals
Language:
En
Journal:
Sci Rep
Year:
2023
Document type:
Article
Affiliation country:
Canada
Country of publication:
United kingdom